Mandibular abnormalities are a common finding in craniofacial disorders. Patterning of first branchial arch development is the result of a complex series of epithelial-mesenchymal interactions. The epithelium establishes the patterning of odontogenesis within the first arch by inductive interaction with mesenchyme. The exact nature of the inductive signal and the manner in which the pattern is established are not known. Retinoids have been proposed as endogenous morphogens in developing systems and if applied at high concentrations affect the patterning of odontogenesis. A link between retinoids and EGF/TGF-alpha has been established in the teratogenic effects of retinoids on palate formation. The expression of EGF mRNA has been characterized in preliminary experiments in the mouse mandible during the period when the pattern of odontogenesis is established. Antisense oligomers to the EGF mRNA were used to demonstrate the necessity of EGF for the initiation of odontogenesis. Furthermore, the effects of retinol on the patterning of the dental lamina in vitro have been characterized and an effect of retinol on the proliferation of mandibular epithelium and the expression of EGF mRNA have been shown in vitro. The purpose of this project is to further explore the role of retinoids in the patterning of odontogenesis and the effects of retinoids on EGF/TGF-alpha/EGF receptors in this process. The effects of retinoids on the spatial distribution and levels of expression of EGF, TGF- alpha/EGF receptor mRNAs and proteins will be studied by in-situ hybridization, Northern and dot blot analysis, quantitative PCR, autoradiography and immunohistochemistry. The distribution of cellular (CRABP, CRBP) and nuclear receptor (RAR's) mRNAs will be studied relative to the forming dental lamina by in situ hybridization and these distributions will be compared with the morphological observations of the effects of retinol and retinoic acid on the pattern of the dental lamina. Antisense oligomers will be used to examine the roles EGF, TGF-alpha, EGF receptors, CRABP, CRBP and RAR alpha/beta/gamma in the initiation and patterning of the dentition.